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Disease Profile

Mucopolysaccharidosis type VI

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Childhood

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ICD-10

E76.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

MPS VI; Mucopolysaccharidosis type 6; MPS 6;

Categories

Metabolic disorders

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 583

Definition
Mucopolysaccharidosis type 6 (MPS 6) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B (ASB) leading to the accumulation of dermatan sulfate.

Epidemiology
Birth prevalence is between 1 in 43,261 and 1 in 1,505,160 live births.

Clinical description
The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The characteristic skeletal dysplasia includes short stature, dysostosis multiplex and degenerative joint disease. Rapidly progressing forms may have onset from birth, elevated urinary glycosaminoglycans (GAG, generally >100 microgram/mg creatinine), severe dysostosis multiplex, short stature, and death before the 2nd or 3rd decades. A more slowly progressing form has been described as having later onset, mildly elevated glycosaminoglycans (generally <100 microgram/mg creatinine), mild dysostosis multiplex, with death in the 4th or 5th decades. Other clinical findings may include cardiac valve disease, reduced pulmonary function, hepatosplenomegaly, sinusitis, otitis media, hearing loss, sleep apnea, corneal clouding, carpal tunnel disease, and inguinal or umbilical hernia. Although intellectual deficit is generally absent in MPS 6, central nervous system findings may include cervical cord compression caused by cervical spinal instability, meningeal thickening and/or bony stenosis, communicating hydrocephalus, optic nerve atrophy and blindness.

Etiology
The disorder is transmitted in an autosomal recessive manner and is caused by mutations in the ARSB gene, located in chromosome 5 (5q13-5q14). Over 130 ARSB mutations have been reported, causing absent or reduced arylsulfatase B (ASB or N-acetylgalactosamine 4-sulfatase) activity and interrupted dermatan sulfate and chondroitin sulfate degradation.

Diagnostic methods
Diagnosis generally requires evidence of clinical picture, ASB activity of less than 10% of the lower limit of normal in cultured fibroblasts or isolated leukocytes, and demonstration of a normal activity of a different sulfatase enzyme (to exclude mucosulfatidosis, see this term). The finding of elevated urinary dermatan sulfate with the absence of heparan sulfate is supportive.

Differential diagnosis
In addition to multiple sulfatase deficiency, the differential diagnosis should also include other forms of MPS (MPS 1, 2, 4A, 7), sialidosis and mucolipidosis (see these terms).

Management and treatment
Before enzyme replacement therapy (ERT) with galsulfase (Naglazyme®), clinical management was limited to supportive care and hematopoietic stem cell transplantation. Galsulfase is now widely available and is a specific therapy providing improved endurance with an acceptable safety profile.

Prognosis
Prognosis is variable depending on the age of onset, rate of disease progression, age at initiation of ERT and on the quality of the medical care provided.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the metaphysis
Abnormality of the wide portion of a long bone
0000944
Chronic otitis media
Chronic infections of the middle ear
0000389
Coarse facial features
Coarse facial appearance
0000280
Disproportionate short-trunk short stature
Disproportionate short-trunked dwarfism
Disproportionate short-trunked short stature
Short-trunked dwarfism

[ more ]

0003521
Epiphyseal dysplasia
Abnormal development of the ends of long bones in arms and legs
0002656
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Mucopolysacchariduria
0008155
Opacification of the corneal stroma
0007759
Recurrent upper respiratory tract infections
Recurrent colds
0002788
Sinusitis
Sinus inflammation
0000246
Thick lower lip vermilion
Increased volume of lower lip
Plump lower lip
Prominent lower lip

[ more ]

0000179
Thick nasal alae
0009928
30%-79% of people have these symptoms
Broad ribs
Wide ribs
0000885
Genu valgum
Knock knees
0002857
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hernia
0100790
Kyphosis
Hunched back
Round back

[ more ]

0002808
Ovoid vertebral bodies
0003300
Short neck
Decreased length of neck
0000470
Splenomegaly
Increased spleen size
0001744
5%-29% of people have these symptoms
Abnormal heart valve morphology
0001654
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue

[ more ]

0000158
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505
Percent of people who have these symptoms is not available through HPO
Anterior wedging of L1
0008432
Anterior wedging of L2
0011941
Autosomal recessive inheritance
0000007
Avascular necrosis
Death of bone due to decreased blood supply
0010885
Cardiomyopathy
Disease of the heart muscle
0001638
Cervical myelopathy
0002318
Constrictive median neuropathy
0012185
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Dermatan sulfate excretion in urine
0008301
Dolichocephaly
Long, narrow head
Tall and narrow skull

[ more ]

0000268
Dysostosis multiplex
0000943
Flared iliac wings
0002869
Glaucoma
0000501
Hepatomegaly
Enlarged liver
0002240
Hip dysplasia
0001385
Hirsutism
Excessive hairiness
0001007
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypoplasia of the odontoid process
0003311
Hypoplastic acetabulae
0003274
Hypoplastic iliac wing
0002866
Inguinal hernia
0000023
Lumbar hyperlordosis
Excessive inward curvature of lower spine
0002938
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Metaphyseal irregularity
Irregular wide portion of a long bone
0003025
Metaphyseal widening
Broad wide portion of long bone
0003016
Prominent sternum
0000884
Split hand
Claw hand
Claw hand deformities
Claw hands
Claw-hand deformities
Split-hand

[ more ]

0001171
Umbilical hernia
0001537

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    FDA-Approved Treatments

    The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

    • N-acetylgalactosamine-4-sulfatase, recombinant human(Brand name: Naglazyme) Manufactured by BioMarin Pharmaceutical, Inc.
      FDA-approved indication: For patients with mucopolysaccharidosis VI. Galsulfase has been shown to improve walking and stair-climbing capacity.
      National Library of Medicine Drug Information Portal

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Mucopolysaccharidosis type VI. Click on the link to view a sample search on this topic.